BLOGS

Category: Brains

In May I wrote in Discover about a major experiment in neuroscience. Ahmad Hariri, a neuroscientist at Duke, is gathering lots of data from hundreds of college students–everything from genetic markers to psychological profiles to fMRI scans. He hopes that the Duke Neurogenetics Study, as he’s dubbed it, will reveal some of the ways in which the variations in our genes influence our brain circuitry and, ultimately, our personality and behavior.

Hariri plans to collect data from over 1000 people, but he and his colleagues are already starting to analyze the hundreds of students they’ve already examined to look for emerging patterns. In the open-access journal Biology of Mood and Anxiety Disorders, they’ve just published some of their first results. While the results are, of course, preliminary, they do offer an interesting look at the future of neuroscience. Rather than pointing to some particular gene or brain region to explain some feature of human behavior, neuroscientists are learning how to find patterns that emerge from several factors working together.

For their new study, Hariri and his colleagues looked in particular at problem drinking. They hoped to find factors that predicted whether students would start imbibing worrisome amounts of alcohol. Other scientists have previously found evidence that a stressful event–the death of a parent, failing a class, and such–sometimes leads students to hit the bottle. But plenty of students endure these hardships and don’t end up getting drunk so often. Hariri and his colleagues suspected that the difference might have to do with how our brains respond to both stress and alcohol.

When they sifted through their data from 200 students, they found two factors helped predict whether a student was a problem drinker or not. One was how strongly their brains responded to rewards. Hariri and his colleagues tested this reward response by having students play a guessing game while having their brains scanned. They had to guess the value of a number on a card, and then they saw whether they got it right or not. Success brought a surge of blood to a region of the brain called the ventral striatum–a region that responds to many pleasures. Recovering alcoholics who see a picture of a bottle will experience a surge in the ventral striatum, for example. The surge was stronger in some students than others. Students who had a stronger surge in the ventral striatum had higher levels of problem drinking in the wake of stressful events.

But that wasn’t the whole story, Hariri found. There was one more requirement. In another test, he and his colleagues tested how people’s brains responded to fearful images–pictures of scared faces, for example. Such sights usually trigger a surge of activity in a region called the amygdala. And some people have a stronger response there than others to the same picture. Hariri found that people with a strong reward response started drinking after a stressful event if they also had a weak response from the amygdala to fearful images.

The suffering that comes from losing a job or being assaulted can lead people to seek solace through alcohol. Hariri’s research suggests that the stronger a reward a person experiences from a drug like alcohol, the more they’ll drink. But that’s not the case if a high-reward person also has a high fear response in the amygdala. A person with a strong amygdala response may feel anxiety about the dangers of getting too drunk and back away from problem drinking. If people don’t sense the threat so keenly, however, then they may have nothing standing in the way of taking in too much alcohol. The scientists found this three-way interaction between stress, reward, and threat when they looked at students who were problem drinkers at the time of the study, and they also found it when they followed up three months later and discovered some of their students had developed a new drinking problem.

As with any study like this, we’ll have to wait and see if it gets supported by replicated studies. Hariri himself will be able to run that sort of study when he has collected more data from other students. If it holds up, scientists may eventually be able to find gene variants that are associated with the high-reward low-threat brain. Some studies even have suggested that a single variant can produce both changes. Perhaps a report from a DNA-sequencing company might include a list of the variants that make some people more prone to drink in stressful situations. On the other hand, it’s also possible that the problem drinking among the students came first, and led to their experiencing stressful events. Teasing apart all the strands will take some time.

PS: For the data geeks, here’s a figure from the paper. The brain in (A) shows the reward-related activity in the ventral striatum. B shows the amygdala’s response to fear. The graphs show how likely people are to experience problem drinking after a stressful event. The left graph shows the response from people with a low reward response from the ventral striatum, and the graph to the right shows high-responders. In each graph, the scientists break out the high amygdala response (green line) and low (blue). The one line that stands out belongs to the high-reward, low-threat subjects.

I was recently invited to write an essay for a promising new web site that launches today, called Being Human. It’s all about what it means to be Homo sapiens, and I chose to focus on our brain, which is so fundamental to our unique place in the natural world. In fact, we like to think of ourselves as our brains. You could, after all, imagine yourself as just a brain in a vat. It might be hard to manage, but if someone could figure out the right liquids to put in the tank and the right wires to stick into it, it “ought” to work. Hence, The Matrix.

This is actually a new notion, and in my essay, I take a look at our ideas about the brain over the past couple thousand years. Check it out.

I’ve brought together some of my favorite pieces about the brain in two ebooks, Brain Cuttings: Fifteen Journeys Through the Mind, and More Brain Cuttings: Further Explorations of the Mind. Earlier this year, the distributor for the ebooks, IPG, got into an ugly fight with Amazon, which led to Amazon yanking IPG’s 5,000 ebooks. Which was a bummer. Just recently, though, the two sides came to an agreement. (The details are here.)

We’ve all heard about tapeworms getting into the intestines. That’s bad enough. But sometimes they can also end up in the brain. In my column in the latest issue of Discover, I write about neurocysticercosis, which is shockingly common in some parts of the world, causing an estimated five million cases of epilepsy. Yet neurocysticercosis experts consider the disease as a fairly easy one to wipe out. We have the tools to do it, but not the will. Check it out.

We’ve learned a lot about how the brain works from functional magnetic resonance images. I should clarify: we’ve learned a lot about the human brain. Thousands of people have volunteered to lie down inside fMRI scanners and have the activity in their brains monitored as they perform different kinds of mental tasks, or even just do nothing at all. We must resist the temptation to look at the pretty fMRI images and think they’re just photographs of the mind. They’re actually more like very complex, statistically worked-over graphs. But even with those caveats, there’s a lot to learn from them. But fMRI only works if you hold very, very still. Having been scanned myself for a story a few years back, I can vouch that this experience takes a lot of patience, and a high tolerance for loud buzzing noises and for narrow, confined spaces. Scientists have managed to take fMRI scans of monkeys and rats, but they’ve either been knocked out cold, or restrained so the images of their brains don’t blur. If you can persuade a gorilla to lie peacefully in the bore of a scanner for half an hour and look at pictures of bananas, do let us know.

All of which is to say that it’s delightful to read a paper just published today in PLoS One in which Emory University scientists report the first successful fMRI scan of unrestrained dogs. The dogs they studied were a border collie named McKenzie and a mutt named Callie. The scientists trained the dogs to jump into the fMRI bore and set their chin on a rest, so that they were staring out the open end. A human handler, standing outside the bore, then made a hand signal. If the left hand was raised, that meant the dogs would get a hot dog after the session. If both hands pointed to each other, that meant no treat. Regardless of the signal, the dogs had to stay motionless in the bore for ten seconds. The hanlder would then give the dog a treat if one had been indicated.

It turned out that the dogs kept their heads still enough that the scientists could line up scans of different trials. And that meant that they could do some comparisons of the activity inside the dogs’ brains when the handler indicated a hot dog was on the way and when the handler indicated it wasn’t. A huge amount of research on humans and lab animals has pointed to one region in particular as being important for perceiving these kinds of rewards, known as the ventral striatum. It releases the neurotransmitter dopamine, which heightens attention throughout the brain. So the scientists focused their attention on the ventral striatum of the dogs.

Of course, dog brains are shaped differently than human brains, so finding it took some work. But once they did, they found a satisfying pattern: when the handler made the hot dog sign, the ventral striatum showed higher levels of activity. (In this picture it’s marked CD, standing for the caudate cluster, in which the ventral striatum is located.) When the handler made the no-hot-dog sign, on the other hand, the ventral striatum remained quiet. Interestingly, McKenzie the border collie had a much stronger response than Callie.

That may be no coincidence, because McKenzie has had lots of agility training in her life. The pathways for learning rewards and responding to them–particularly from humans–may be stronger in her brain. Which raises an important question: what’s the nature of the reward in a dog’s brain? Is it the prospect of the hot dog alone that triggers the response, or does pleasing a human by doing a drill correctly play a part? As I wrote in this Time story in 2009, a new field called canine cognition is taking shape to address these questions. Until now, canine cognition studies have been limited to basic psychological experiments, such as seeing how well dogs can make sense of a pointed hand. Now we can start to see what’s happening inside the canine brain during some of those experiments as well.

If there’s ever excuse to publish an optical illusion as cool as the “Rotating Snakes,” I’ll take it. This illusion was invented in 2003 by Akiyoshi Kitaoka of Ritsumeikan University in Japan, and ever since, Kitaoka and other scientists have been trying to figure out why it works. A new paper by Stephen Macknik at the Barrow Neurological Institute in Phoenix may have the answer.

As you’ll notice, the circles seem to rotate in response to where you look at the illusion. So Macknik and his colleagues tracked the movement of people’s eyes as they gazed at two of these wheels on a computer screen. Their subjects kept a finger pressed on a button, lifting it whenever they seemed to see the wheels move.

Macnick and his colleagues found a tight correlation between the onset of the illusion and a kind of involuntary movement our eyes make, known as microsaccades. Even when we’re staring at a still object, our eyes keep darting around. These movements, called microsaccades, help us compensate for a peculiar property of the eye: if we stare at an object for too long, the signals each photoreceptor sends to the brain become weaker. Microsaccades refresh the photoreceptors with a different input and breath new life into our perception.

Unfortunately, the jumps of our eyes get in the way of our perception of motion. If we see a snake slithering along in a desert, we don’t have to register an entire image of the snake at one instant, then another image at the next instant, and then compare the location of the two images, in order to figure out that the snake is on the move and we might want to jump out of the way. Instead, we only have to sense rapidly changing light patterns in neighboring parts of the eyes. If certain neurons in the vision-processing regions of the brain gets a sudden, strong signal from the eye, they register motion.

Normally, our eyes can register motion despite the fact that they are also performing microsaccades. Our brains can tell the difference between a shift brought on by the movement of an object and one brought on by the movement of our own eyes. But thanks to the strong contrasts and shapes in the Rotating Snakes Illusion, we get mixed up. Our motion sensors switch on, and the snakes start to slither.

I’ve got a new column in Discover on a scientist tracing the links from our genes to our personality. Here’s how it starts:

Ahmad Hariri stands in a dim room at the Duke University Medical Center, watching his experiment unfold. There are five computer monitors spread out before him. On one screen, a giant eye jerks its gaze from one corner to another. On a second, three female faces project terror, only to vanish as three more female faces, this time devoid of emotion, pop up instead. A giant window above the monitors looks into a darkened room illuminated only by the curve of light from the interior of a powerful functional magnetic resonance imaging (fMRI) scanner. A Duke undergraduate—we’ll call him Ross—is lying in the tube of the scanner. He’s looking into his own monitor, where he can observe pictures as the apparatus tracks his eye movements and the blood oxygen levels in his brain.

Ross has just come to the end of an hour-long brain scanning session. One of Hariri’s graduate students, Yuliya Nikolova, speaks into a microphone. “Okay, we’re done,” she says. Ross emerges from the machine, pulls his sweater over his head, and signs off on his paperwork.

As he’s about to leave, he notices the image on the far-left computer screen: It looks like someone has sliced his head open and imprinted a grid of green lines on his brain. The researchers will follow those lines to figure out which parts of Ross’s brain became most active as he looked at the intense pictures of the women. He looks at the brain image, then looks at Hariri with a smile. “So, am I sane?”

Hariri laughs noncommitally. “Well, that I can’t tell you.”

True enough: On its own, Ross’s brain can’t tell Hariri much. But a thousand brains? That’s another matter. Hariri is in the midst of assembling a large cohort of Duke undergraduates and gathering key information—brain scans, psychological tests, and genetic markers—for the Duke Neurogenetics Study. From this mountain of data, Hariri believes he’ll be able to learn a lot about Ross, about himself, about all of us. As a result, someday he may be able to read your DNA and determine your innate level of anxiety, your propensity for drinking, and a range of other psychological traits.

Tomorrow (April 2) Robert Krulwich of Radiolab and I will be at Columbia University to moderate a debate about the future of neuroscience. Entitled, “Does the brain’s wiring make us who we are?” it will bring together Sebastian Seung of MIT and Anthony Movshon of NYU.

The auditorium filled up less than two hours after the tickets were made available online a few weeks ago, and a hefty waiting list quickly took shape. Fortunately, the organizers have made it possible for more people to watch the neurological fireworks. If you’d like to see a live simulcast, you can sign up for a free seat in nearby Pupin Hall 301. Here’s the Eventbrite page where you can grab yours.

If you can’t make it there in person, you can join us in cyberspace by catching the livestream on the Radiolab web site.

And if you want to tweet the debate or follow it on Twitter, please use the hashtag #brainbrawl (I decided #igotyourconnectomerighthere would take up too much space…)

If you’d like get ready for the debate by reading about its origins, here are some places to start:

Update: Zen Faulkes has a review of Seung’s new book, Connectome, at his blog, NeuroDojo. It follows up on a previous post that Bora Zivkovic reminded me of in the comments, “Overselling the Connectome.”

Our 80 billion neurons form an estimated 100 trillion connections. Through those links surge the signals that make thought possible. Sebastian Seung of MIT has been calling for a full-blown atlas of those connections, because he believes it will help us understand how the brain works and how the brain makes us who we are. In the April issue of Discover, I pay a visit to Seung’s lab to see what he’s up to, and what he hopes for the future. Check it out.

I couldn’t be happier that this column is available a couple weeks before Seung will participate in a public debate about the connectome on April 2, hosted by myself and Robert Krulwich of Radiolab. The tickets were all snapped up about an hour and a half after becoming available online, but I will certainly report back afterwards about how it went.

What will be the next big breakthrough in neuroscience? What will finally explain how brains work, how they fail in disease, and what makes us each unique? Some neuroscientists believe that research would be radically accelerated by finding and deciphering “connectomes,” maps of connections between neurons. Funding agencies are wagering millions of dollars on the idea that connectomics will be as fundamental to neuroscience as genomics is to molecular biology.

But others disagree, arguing that maps of the brain by themselves cannot offer much insight into how this remarkable organ does its job. Just as a genome by itself is only a blueprint with little power to explain how an organism works, a connectome is at best a framework with little power to explain brain function. Should neuroscience make it a priority to launch a significant connectomics program, diverting human and financial resources from other worthy goals?

Join us as leading “connectomist” Dr. Sebastian Seung defends his position in public against the formidable neurophysiologist Dr. Anthony Movshon. Award-winning science writer Carl Zimmer teams up with co-creator of NPR’s Radiolab, Robert Krulwich, to moderate this debate on neural cartography, guiding the audience through both known and unknown territory as we ask the question: Are brain maps the future of neuroscience or an empty promise?